Reversing the Warburg Effect: Metabolic Modulation as a Novel Cancer Therapy
Despite the research efforts and enormous investments from the industry and the public, oncology has an impressively poor success rate in the clinical development of effective investigational drugs; less than a third of that in cardiovascular or infectious diseases (Kamb et al.2007). Traditionally, oncology drug development has focusedessential targets (i.e. essential for the survival of all dividing cells). This approach suffers from low selectivity and thus narrow therapeutic windows. In contrast, more selectivity is achieved by targeting nonessential targets, but as expected, this approach suffers from poor efficacy. It is extremely rare to find a target that is essential only to cancer cells; the dependence of chronic myelogenous leukemia cells on Ableson kinase is induced by a chromosomal translocation only in the malignant cells, making the efficacy and selectivity of imatinib, anexception in experimental oncology (Kamb et al.2007).
The biggest challenges in cancer...
KeywordsPeripheral Neuropathy Mitochondrial Membrane Potential Lactic Acidosis Glucose Oxidation Aerobic Glycolysis
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